Optochemical sensors have been used to an increasing extent for measuring a great variety of fluids such as gases, liquids or even, mixtures thereof, both in the medical, biological or biochemical field and in the food and other laboratory or industrial sectors in order to enable the rapid and reliable detection of the presence or absence of specific substances. Gases whose presence or absence is determined by such sensors, for instance, include oxygen, CO2, but also, for instance, ozone or ammonia. Furthermore, such sensors have allowed, for instance in the medical field by measuring biomolecules or pathogenic substances, to draw conclusions on, for instance, wound healing, wound contamination, the presence or absence of certain pathogens or the like, in that they are, for instance, employed for measuring pH values, which can be used for conclusions on such processes.
The operating principle of optochemical sensors basically relies on the interaction of a substance excitable by light with the analyte to be measured, wherein the excitable substance is excited by light of a specific, suitable wavelength and the molecules, after having been excited, emit the absorbed energy in the form of fluorescence light when returning into their original state, which fluorescence light is extinguished by interactions with the analyte. In order enable the detection of such an extinction of the fluorescence light, it is necessary, on the one hand, for the fluorescence light to have sufficient intensity and, on the other hand, for the non-extinguished fluorescence light to be reflected onto a detector, which will detect the presence or absence of an analyte based on the measurement of the intensity of the fluorescence light.
The substance to be excited by the radiated light is usually a so-called fluorophore, which, during the use of such an optochemical sensor, is either in direct contact with the substance to be measured or is protected from noxious environmental influences by a cover permeable to the substance to be detected. During the operation of such a sensor, the fluorophore is usually radiated from the side facing away from the substance to be measured, excited, and the non-extinguished fluorescence light is absorbed or captured on a suitable detector also facing away from the sample to be measured and/or provided in a housing protected from the sample to be measured, optionally amplified, and subsequently measured.
In particular when using such sensors in the medical or biological field, it is essential that the sensors are dimensioned as small as possible and that they can preferably be used in so-called micro total analysis systems (TAS).
Thus, in particular the question of the size of such sensors has become more and more important, since recently not only the range of application of such sensors has grown tremendously but also attempts have, for instance, been made to enable without special expenditure in small-structured, e.g. medical, equipment in addition to other required activities such as, e.g. in connection with catheters, the introduction of tools into wounds, or of optical devices for in-situ observation or the like, the direct detection of, for instance, the presence or absence of analytes to be assayed; it has turned out to be especially essential and important that such sensors can be miniaturized or optionally be built so small as to be integratable into microchips or mountable on printed circuit boards, which cannot be achieved by systems available at present.
The integration of such optochemical sensors in chips involves the recurring problem that the sensors require a separation of the fluorescence light from the excitation light by means of a spectrometer or by using optical filters, which has turned out to be unsatisfactory, since the intensity of the excitation light is usually significantly higher than the intensity of the generated fluorescence light, which constitutes a problem for the measuring accuracy, in particular in miniaturized systems, since stray light might disturb or falsify measurements.
US 2008/0180673 A1 describes a test system including an optical medium, a binding agent and a light, detector. The optical medium provides a light path and the binding agent is positioned so as to hold a target complex in an evanescing field formed by the propagation of light along the light path. Due to the interaction of the complex with the evanescing field, light is emitted, which is impinges on a detector positioned for the detection of the light.
From U.S. Pat. No. 6,448,064 B1, a miniaturized DNA biosensor can be taken, which is designed to detect specific molecular targets like nucleic acids. The miniaturized biosensor is a chip comprising multiple biological sensing elements, excitation microlasers, a sampling waveguide equipped with optical detectors, integrated electro-optics, and a biotelemetric radiofrequency signal generator. Such a device is suitable for gene analysis.
From US 2005/0237518 A1, an optical sensor device for determining the presence or concentration of an analyte can be taken, coprising a waveguide disposed over a light source and a light detector mounted on a surface of a substrate and separated from the light source, wherein the waveguide has a thickness corresponding to a far-field emission point of the light source. An analyte indicator matrix is, moreover, disposed on the outer surface of the waveguide.
From US 2002/016413 A1, an electro-optical sensing device for detecting the present or concentration of an analyte in a liquid or gaseous medium can be taken, which device included a pair of indicator elements positioned to receive radiation from a radiation source transmit said radiation to a pair of photosensitive elements.
US 2006/0197960 A1 finally discloses a biochip for testing biological substances, comprising a plurality of binding sites, optical means for determining a specific binding event at each binding site, wherein the plurality of binding sites and the means for determining are integrated in a single chip which is electrically powered and produces signals in response to the binding events at each binding site.